MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Positron emission tomography (PET) combined with fludeoxyglucose F18 (FDG) is currently recommended for the noninvasive diagnosis of lung nodules suspicious for lung cancer. Our investigation adds to growing evidence that FDG-PET scans should be interpreted with caution in the diagnosis of lung cancer. Misdiagnosis of lung lesions driven by FDG-PET avidity can lead to unnecessary tests and surgeries for patients, along with potentially additional complications and mortality.

To estimate FDG-PET diagnostic accuracy, we conducted a multi-center retrospective cohort study. The seven cohorts originating from Tennessee, Arizona, Massachusetts and Virginia together comprised 1188 nodules, 81 percent of which were malignant. Smaller nodules were missed by FDG-PET imaging. Surprisingly, negative PET scans were also not reliable indicators of the absence of disease, especially in patients with smaller nodules or who are known to have a high probability of lung cancer prior to the FDG-PET test.

Our study supports a previous meta-analyses that found FDG-PET to be less reliable in regions of the country where fungal lung diseases are endemic. The most common fungal lung diseases in the United States are histoplasmosis, coccidioidomycosis and blastomycosis. All three fungi reside in soils. Histoplasmosis and blastomycosis are common across much of the Mississippi, Ohio and Missouri river valleys and coccidioidomycosis is prevalent in the southwestern U.S. These infections generate inflamed nodules in the lungs (granulomas), which can be mistaken for cancerous lesions by imaging.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Lung cancer is leading cause of cancer-related mortality, and detecting it in earlier stages is crucial to improving outcomes for patients. The motivation for this study lies in understanding the phenotypic and genetic make-up of lung cancer during its early stages, using a blood sample (blood biopsy). We have done this by employing a microfluidic device to capture cancer cells circulating in the blood that is obtained from the peripheral veins and the pulmonary vein (a vein next to the tumor itself) from patients with early stage lung cancers. The idea behind using blood from the pulmonary vein was to obtain a richer yield of these circulating tumor cells, which are rare in the blood.

Through this study, we found that the pulmonary vein does yield a much higher quantity of circulating tumor cells, and also often harbors these cells in large clusters. We further went on to study the significance of these clusters, and found that these clusters indicated aggressive traits such as resistance to treatment, and could also potentially suggest poorer patient outcomes at long term.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Most long-term survivors of lung cancer are among the patients who were fortunate enough to be identified early enough to undergo curative-intent surgery. In the US, 60,000 individuals undergo curative-intent surgery for lung cancer every year. This number is likely to increase over the next few years as lung cancer screening becomes more widely adopted. Unfortunately, fewer than 50% of patients who undergo curative-intent surgery actually survive up to 5 years.

We show that the quality of surgery, especially the quality of pathologic nodal staging is a powerful driver of survival differences between groups of patients. In general, pathologic nodal staging (important as it is stratifying patients into risk groups so those at high risk can be offered additional treatments to increase the chances of cure while those at truly low risk can be left alone without exposure to cost and side-effects of additional treatments) is very poorly done. We show how the percentage of patients whose pathologic staging met sequentially more stringently-define thoroughness of staging metrics falls off sharply, while the survival sequentially increases.

Response: Checkpoint inhibitors (CPIs) have recently transformed the management of patients with metastatic lung cancer, demonstrating significant improvements in overall and progression-free survival in both the first-line setting in patients with increased expression of PD-L1 (≥50%) and in patients with previously treated NSCLC who have progressed on chemotherapy. CPIs are also moving into the treatment of patients with localized lung cancer, with the recently published PACIFIC trial demonstrating a significant improvement in progression-free survival in patients with inoperable stage III NSCLC treated with adjuvant durvalumab after definitive chemoradiotherapy.

However, CPIs are associated with unique toxicities as compared to cytotoxic chemotherapy, including pulmonary, endocrine, neurologic, gastrointestinal, and dermatologic adverse events, which may be fatal in some cases. The risk of autoimmune pneumonitis with checkpoint inhibitors is estimated to be on the order of 5%. Many patients with lung cancer will require radiotherapy for palliation of symptoms. Thoracic radiotherapy (TRT) is also a risk factor for pneumonitis, with a dose- and volume-dependent impact on risk. However, it is unknown whether treatment with CPIs and TRT is associated with increased risk of toxicity.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Prior literature has been suggestive of both a protective and harmful effect of certain B vitamins on lung cancer risk. We wanted to examine the association of intakes of vitamins B6, folic acid (B9), and B12 from supplements –which are typically taken at very high doses– and lung cancer risk in a large, prospective study of 77,000 men and women living in Washington State. The study is unique as it was designed specifically to examine associations of dietary supplements with cancer occurrence. We found that men who took high doses of vitamin B6 and B12 from individual supplements over a long period of time (meaning, doses much higher than the US RDA and much greater than what one would receive from taking a multivitamin over the long term) were at nearly 2-fold increased risk of lung cancer compared to men who did not have B6 or B12 intake from any supplemental source. This finding of increased risk appeared to be specific to men who were current smokers. Among them, long term high-dose supplementation was associated with 3-4 fold increases in lung cancer risk. We observed no increased risk for any of the supplements – B6, B12, or folic acid – with lung cancer risk in women or women who smoked.

Prof. Gerhard HamiltonDepartment of Obstetrics and Gynecology
Medical University of Vienna

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Small cell lung cancer (SCLC) is a highly aggressive tumor (15 % of all lung cancers) mainly of patients with high tobacco consumption which shows an extremely poor survival (< 5% 2-year survival rate). Unfortunately the
low survival rates of advanced SCLC cases has not improved significantly during the last decades, with platinum drugs/etoposide and topotecan employed for first- and second-line chemotherapy, respectively. All kinds of new chemotherapeutics, targeted drugs and immunotherapies either failed or resulted in prolongation of survival of several months at best. SCLC responds well to first-line therapy but relapses within a short time as chemoradioresistant tumor. The failure of hundreds of registered studies seem to be linked to the lack of knowledge of the mechanism of resistance of SCLCs and proper ways to reverse the refractoriness.

Small cell lung cancer is distinguished by excessive numbers of circulating tumor cells (CTCs) in advanced stages. CTCs contain the founder of metastasis and seem to constitute a highly chemoresistant cell population. Thus, we ware able to establish a panel of permanent CTC lines in vitro for the first time (8 SCLC lines so far from blood samples). Although CTCs were considered to be chemoresistant we detected that they are chemosensitive in vitro in form of single cell suspensions. However, all CTC lines developed spontaneously into large multicellular aggregates, termed tumorospheres, which grow up to 1-2 mm in size and exhibit high chemoradioresistance due to limited drug perfusion as well as content of quiescent and hypoxic cells. Resistance to irradiation seems to be caused by lack of oxygen, such limiting the generation of oxygen radicals. High resistance mediated by the occurrence of tumorospheres easily explains the failure of a large number of drugs – if one is not able to achieve a sufficient concentration of a drug in cancer cells and the cells are quiescent, the respective compounds will not be able to destroy the target cells, regardless of their chemical nature.

Response: In the last few years some new therapies targeting immune checkpoints have been developed. The programmed death receptor-1 (PD-1) are immune checkpoints that prevent the immune system to act against own tissues. By blocking these mediators it is possible to prevent tumors to escape from the immune system.

About half of the patients receiving these therapies will develop mild to moderate cutaneous adverse events. In the pre-authorization studies for malignant melanoma these include rash, vitiligo, and pruritus. “Rash” has commonly been reported as an adverse event in many oncologic trials evaluating the drugs, without providing further information about the clinical or histological details. Lately, lichenoid eruptions associated to these therapies have been reported and it suggests that an important percentage of these reactions present lichenoid histological features.

MedicalResearch.com: What do we know about the health effects of cigarette filters? Response: The issue is that the design of the filters makes a cigarette even more dangerous, which can be regulated by the FDA. The issue is not about having a filter, but how they are made. And now we are changing the dialogue to the design of virtually all cigarettes. The holes on the filter are likely one reason the cigarettes of today are more dangerous.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Identifying specific genetic mutations in non-small cell lung cancer patients helps clinicians choose the best treatment options; specific therapies that target mutations can improve patient outcomes, including reducing the risk of death or lessening the severity of the disease. However, nearly 80% of cancer patients do not have genetic mutation results available at initial oncology consultation; up to 25% of patients begin treatment before receiving their results. These factors hinder physicians’ ability to pursue optimal treatment strategies.

This study found that a blood-based assay, the GeneStrat test, provides results in 72 hours for 94% of patients, which expands testing options, and supports faster treatment decisions by physicians.

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